Resilient Brains: Alzheimer's Changes Without Symptoms
Author: Netherlands Institute for Neuroscience - KNAW
Published: 15 May 2024 - Updated: 4 Nov 2026
Publication Details: Peer-Reviewed | Findings
Table of Contents:
Synopsis - Definition - Overview - FAQs - Insights, Updates - Related Content
Synopsis
This research from the Netherlands Institute for Neuroscience, peer reviewed and published in 2024, studied brain tissue from the Netherlands Brain Bank, which holds samples from more than 5,000 donors along with detailed medical histories. The team identified just 12 donors whose brains showed Alzheimer's disease changes but who had no memory or thinking problems while alive, a rare resilient group. Compared with people who had Alzheimer's symptoms, these donors had more of the antioxidant metallothionein made by astrocytes, less activity in an inflammatory microglia pathway, a normal unfolded protein response and signs of more mitochondria. The findings matter because understanding why some brains resist the disease could point to new drugs, and they offer hope to older adults and families affected by dementia.*
At a Glance
- 1 - Only 12 resilient donors were found among more than 5,000 in the brain bank.
- 2 - The researchers say lab and animal studies are needed to show cause and effect.
- 3 - Exercise, mental activity and strong social ties may help delay Alzheimer's symptoms.
- 4 - People with complex jobs may build up more Alzheimer's changes before showing symptoms.
Topic Definition
- Alzheimer's Resilience
Alzheimer's resilience describes the state of people whose brains contain the typical changes of Alzheimer's disease, such as amyloid plaques and tau tangles, but who keep normal memory and thinking during life. Researchers study these individuals to find the genetic, biological and lifestyle factors that protect brain function, in the hope of developing treatments that copy those protective effects.
Overview
Gene-expression profiling of individuals resilient to Alzheimer's disease reveals higher expression of genes related to metallothionein and mitochondrial processes and no changes in the unfolded protein response.
Everyone experiences aging in their own way, and factors such as genetics, lifestyle and environment play a role in this process. Some individuals reach the age of 90 or even 100 in good health, without medications or brain disease. But how do these individuals maintain their health as they age?
Luuk de Vries from Joost Verhaagen's group, and his colleagues Dick Swaab and Inge Huitinga, looked at brains from the Netherlands Brain Bank. The Netherlands Brain Bank stores brain tissue from more than 5,000 deceased brain donors with a wide range of different brain diseases. What makes the Netherlands Brain Bank so unique is that, in addition to the stored tissue with very precise neuropathological diagnoses, they also keep the documented medical history and detailed disease course with the symptoms of each donor.
Resilient Group
The team found a subgroup of people who had Alzheimer's disease processes in their brains, but did not show any clinical symptoms while alive. A so-called 'resilient' group. But how is it possible that they did not experience any symptoms while others did?
Luuk de Vries:
"What is happening in these people at a molecular and cellular level was not clear yet. We therefore searched for donors with brain tissue abnormalities who did not show cognitive decline in the Brain Bank. Of all the donors we found 12, so it is quite rare. We think that genetics and lifestyle play an important role in resilience, but the exact mechanism is still unknown."
Keep Challenging Yourself
"Exercise or being cognitively active and having a lot of social contacts can help in delaying the onset of Alzheimer's disease. It has recently also been found that those who receive a lot of cognitive stimuli, like through a complex job, can build up more Alzheimer's pathology before developing symptoms. If we can find the molecular basis for resilience, then we have new starting points for the development of medication, which could activate processes related to resilience in Alzheimer's patients."
Alzheimer's Versus Resilient Group
"When we looked at gene expression, we saw that a number of processes were altered in the resilient group. First of all, the astrocytes appeared to produce more of the antioxidant metallothionein. Astrocytes are like garbage collectors and provide a protective role for the brain. Astrocytes often also ask for help from microglia, but because they can be quite aggressive, they sometimes worsen inflammation. In the resilient group a microglia pathway that's often linked to Alzheimer's disease appeared to be less active. In addition, we saw that the so-called unfolded protein response, a reaction in brain cells that automatically removes a misfolded toxic protein, was affected in Alzheimer's patients, but was relatively normal in resilient individuals. Finally, we found indicators that there may also be more mitochondria in the brain cells of resilient individuals, which ensures better energy production."
But what do these differences in processes mean? And is there cause or effect?
"It remains difficult to determine from human data which process initiates the disease process. You can only demonstrate this by changing something in cells or animal models and seeing what happens next. That is the first thing we have to do now."
Famous People Who Have or Had Dementia or Alzheimer's Disease: A list of famous and well known people who currently have or had either dementia or Alzheimer's Disease.
Frequently Asked Questions
NOTE: Researched FAQs by Disabled World (DW)
Can you have Alzheimer's disease without symptoms?
Yes, studies of donated brains show that some people have Alzheimer's changes without ever developing dementia. This is sometimes called resilience or asymptomatic Alzheimer's.
What is cognitive reserve?
Cognitive reserve is the brain's ability to cope with damage by using different networks or strategies. It is thought to be built through education, mentally demanding work and social activity.
What do astrocytes do in the brain?
Astrocytes are star-shaped support cells that supply nutrients to nerve cells, clear waste, control inflammation and help maintain connections between neurons.
How can I donate my brain to research?
Many countries have brain banks that accept donors with and without brain diseases. Registering in advance and telling family members is usually required.
Can lifestyle changes lower the risk of dementia?
Research suggests that physical activity, a healthy diet, not smoking, limiting alcohol, treating hearing loss and controlling blood pressure and diabetes can lower dementia risk.
What are amyloid plaques and tau tangles?
Amyloid plaques are clumps of protein between nerve cells, and tau tangles are twisted protein fibers inside them. Both are hallmarks of Alzheimer's disease.
Are there new treatments for Alzheimer's disease?
Drugs such as lecanemab and donanemab, which remove amyloid from the brain, are approved in some countries for early Alzheimer's and can modestly slow decline.
What are mitochondria?
Mitochondria are tiny structures inside cells that produce most of the energy cells need. Brain cells use a great deal of energy, so healthy mitochondria are important.
Insights, Analysis, and Developments
Editorial Note: The gap between what doctors see in the brain and what a person experiences has puzzled dementia researchers for decades, and this resilient group offers a rare window into it. The findings fit the wider idea of cognitive reserve, in which education, mental challenge and social life help the brain keep working despite damage. Because the study is small and based on tissue after death, it cannot yet say which processes cause resilience and which simply accompany it. Meanwhile, the practical advice remains the same for everyone: stay physically active, keep learning, stay connected with others and manage blood pressure, diabetes and hearing loss, all of which are linked to lower dementia risk.*
Attribution/Source(s): This peer-reviewed publication was selected for publishing by the editors of Disabled World (DW) due to its relevance to the disability community. Originally issued as a press release by Netherlands Institute for Neuroscience - KNAW and published on 15 May 2024. Last updated on 4 Nov 2026. This content may have been edited for style, clarity, or brevity.
* Editorial additions by Ian C. Langtree.